MEDLINE, EMBASE, Cancerlit, the Cochrane Controlled Trials Register and the National Research Register (NRR) were searched. The search terms used were presented in the appendix but no dates were given. The review was conducted on behalf of the UK National Institute for Clinical Excellence, which approached the manufacturers (Bristol-Myers Squibb and Aventis) for submissions presenting clinical and economic evaluations of the taxanes. Researchers and research groups identified by the NRR, the Cochrane Breast Cancer Group and the Cochrane Gynaecological Cancer Group were contacted for further information and studies, although not all responded to these requests.

Study selection

Study designs of evaluations included in the review

Specific interventions included in the review

Paclitaxel (taxol) or docetaxel (taxotere) used either alone or in combination with other drugs as part of a chemotherapy regimen for first- or second-line treatment for advanced breast cancer, and paclitaxel used either alone or in combination with other drugs for first-line treatment of ovarian cancer. Adjuvant chemotherapy was not considered. The use of taxanes as part of a high-dose regimen with autologous stem cell support was not considered. Trials comparing different taxane regimens only (in terms of dose, period of administration or combination) were not included. Dosages of paclitaxel and docetaxel, when used as a single agent for breast cancer, ranged from 175 to 200 mg/m2 and 60 to 100 mg/m2, respectively. Combination therapy for the treatment of breast cancer included doxorubicin (50 mg/m2) plus paclitaxel (150 to 220 mg/m2), and docetaxel (75 mg/m2) plus doxorubicin (50 mg/m2). Other comparator chemotherapy regimens used for breast cancer included the combination of cyclophosphamide (100 mg/m2), methotrexate (40 mg/m2), fluorouracil (600 mg/m2) plus prednisone; doxorubicin (60 mg/m2) plus cyclophosphamide (600 mg/m2); mitomycin (12 mg/m2) plus vinblastine (6 mg/m2); methotrexate (200 mg/m2) plus fluorouracil (600 mg/m2); fluorouracil (750 mg/m2) plus navelbine (25 mg/m2); or the single agents mitomycin (12 mg/m2) or doxorubicin (75 mg/m2). For the treatment of ovarian cancer, paclitaxel was used as a single agent (200 mg/2) or in combination with cisplatin (75 mg/m2) or carboplatin (175 mg/m2), where the dosage used was 135 or 175 mg/m2.

How were decisions on the relevance of primary studies made?

All obtained titles and abstracts were independently assessed for inclusion by two reviewers using a pre-screen form. Any discrepancies were resolved by discussion, and full articles were obtained where possible.

Assessment of study quality

The quality of studies was assessed according to the rating system set out in the NHS cancer guidance reports (See Other Publications of Related Interest nos.1-4). The quality of the included studies was assessed by one reviewer and checked by another.

Data extraction

The data was extracted into an Access database by one reviewer and checked by another. The type of data that were extracted from individual studies was listed in the appendix. The results of individuals studies were presented as relative risk plots (without pooling). Some studies included Kaplan-Meier curves. When raw data were not presented, numbers of patients surviving were estimated from these graphs.

Methods of synthesis

How were the studies combined?

Quantitative syntheses were not undertaken on account of heterogeneity, so the trials were combined in a narrative.

How were differences between studies investigated?

The heterogeneity of studies was assessed by clinical judgements of differences regarding patients, interventions, outcomes, costs and quality.

Results of the review

Fourteen RCTs were included in the review. These included 1 RCT (429 patients) of docetaxel as first-line treatment for breast cancer, 4 RCTs (1,545 patients) of paclitaxel as first-line treatment for breast cancer, 4 RCTs (1,092 patients) of docetaxel as second-line treatment for breast cancer, and 1 RCT (81 patients) of paclitaxel as second-line treatment for breast cancer. There were also 4 RCTs (3,746 patients) of paclitaxel as first-line treatment for ovarian cancer.

Paclitaxel for first-line treatment for breast cancer (4 RCTs):

Three trials looked at single-agent paclitaxel. The median progression-free survival in the paclitaxel arm ranged from 4 to 5.9 months; in no trial was this greater than the control arm. In one trial, the anthracycline group had significantly longer progression-free survival than single-agent paclitaxel (7.5 versus 4.0 months, p=0.0001). The median length of overall survival in the paclitaxel arm ranged from 17.3 to 22.2 months; in no trial was this significantly different to the control. One of these trials compared single-agent paclitaxel with combined paclitaxel plus anthracycline, for which survival was similar in both arms (22.2 versus 22 months).

Two trials looked at the combination of paclitaxel with anthracycline. The median progression-free survival in the intervention arms ranged from 8 to 8.3 months. In both trials this was significantly greater than the control arm (8 versus 6 months, p=0.003; in one trial; 8.3 versus 6.2 months, p=0.034, in the second). The median length of overall survival for patients in the paclitaxel-anthracycline combination arm ranged from 22 to 22.7 months. Patients in the paclitaxel-anthracycline arm survived for significantly longer than control in one trial (22.7 versus 18.3 months, p=0.02) but not in the other (22 versus 18.9 months, p=0.24), although the difference was comparable.

QOL was evaluated in 3 trials (one looking at paclitaxel as a single agent and two looking at paclitaxel in combination with anthracycline). There was no significant difference between paclitaxel and control in any of the trials in terms of overall QOL, although differences were apparent on some subscales. These did not appear to follow a consistent pattern across the trials.

Docetaxel for first-line treatment for breast cancer (1 RCT):

One RCT was identified which was published as an abstract only and of poor quality. A combination of docetaxel and doxorubicin produced a greater overall response than doxorubicin and cyclophosphamide combined, there were no long-term results such as progression-free or overall survival.

Paclitaxel for second-line treatment for breast cancer (1 RCT):

The median progression-free survival in the paclitaxel arm was 3.5 months. This was significantly longer than the mitomycin control arm (1.6 months, p=0.026). The median overall survival in the paclitaxel arm was 12.7 months, compared with 8.4 months in the mitomycin arm. QOL was not reported.

QOL was evaluated in 2 trials. There was no significant difference between docetaxel and control in either of these trials in terms of global health status, although differences were apparent on some subscales. These did not appear to follow a consistent pattern across trials.

Six economic evaluations compared paclitaxel to docetaxel for the treatment of breast cancer. The cost-utility ratios for incremental QALYs gained ranged from £1,990 to £2,431. Three analyses compared docetaxel and vinorelbine for the treatment of breast cancer. The cost-utility ratio for incremental QALYs gained was £14,050 in the only study carried out in the UK.

Nine cost-effectiveness and three cost-utility analyses looked at the use of paclitaxel for first-line treatment for ovarian cancer. Two UK studies used carboplatin plus paclitaxel, for which the range of cost per QALY gained according to the cost-utility analyses was £5,273 to £11,269.

Authors' conclusions

This review is based in currently available evidence, which favours docetaxel in the second-line treatment of advanced breast cancer and paclitaxel in the first-line treatment of ovarian cancer. However, the evidence is not robust for any indication. There are several trials in progress, which will need to be taken into consideration once they have developed sufficiently.

CRD commentary

This was a well-conducted review. The aims were clearly stated with clearly reported inclusion and exclusion criteria. A comprehensive literature search was undertaken (although the dates of databases searched were not presented), which included approaching the manufacturers for unpublished data. A systematic procedure involving one or more reviewers was used to assess the relevancy of retrieved articles and data extraction. The authors also assessed the validity of included trials. Relevant details of included RCTs were clearly presented in tables and described in the text. Differences between included studies were briefly discussed and a narrative synthesis of the results was appropriate. The authors' conclusions follow from the results.

Implications of the review for practice and research

Practice: The authors do not make any recommendations for practice.

Research: The authors state that further recommendations for primary research are premature before the final results of ongoing research are published in full. They also state that updating this systematic review is the most pertinent recommendation at this stage.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.